Browsing by Author "Iwaloye O"

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    Co-administration of metformin and gallic acid modulates JAK/STAT signaling pathway and glutathione metabolism in fructose-fed streptozotocin diabetic Rats
    (2022) Elekofehinti OO; Ariyo EO; Iwaloye O; Obafemi TO
    Background Incidence of diabetes Mellitus (DM) is on the rise with each passing year in spite of available therapies in the management of DM. Metformin, a standard antidiabetic drug, and gallic acid (GA) are some of the compounds with established antidiabetic properties. However, there is dearth of information on their combination on JAK/STAT signaling pathway and glutathione metabolism in diabetic model. This study investigated the combined effect of metformin and GA on diabetic rats. Methods Forty male wistar rats were divided into 5 groups viz: diabetic control, normal control, Metformin (100 mg/kg), GA (100 mg/kg) and GA (100 mg/kg) + Metformin (100 mg/kg). Diabetes was induced by administration of 10% fructose for 14 days followed by injection of streptozotocin (40 mg/kg). The therapy was administered for a total of 21 days. The pancreatic mRNA expression of antioxidant genes (glutamate cysteine ligase catalytic subunits (GCLC), glutamate cysteine ligase modifier subunits (GCLM) and Glutathione Synthetase (GSS), inflammatory genes (tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and proteins of the Janus Kinase/ Signal Transducer and Activator of Transcription pathway (Janus Kinase (JAK), Signal Transducer and Activator of Transcription (STAT), were quantified using reverse-transcriptase polymerase chain reaction (RT-PCR). Metformin and GA were also docked with Insulin, GSS, and Janus Kinase 2 (JAK2) to determine their binding affinity. Results Rats treated with co-administration of GA and metformin significantly (p < 0.05) decreased fasting blood glucose level in comparison with groups treated with gallic acid only and metformin only. The gene expression analysis shows that co-administering metformin and gallic acid protects the pancreas of STZ-induced rats by increasing glutathione production, alleviating inflammation (IL-1, IL-6, IFN-), and modulating the JAK/STAT signaling pathway though upregulation of GCLC, GCLM, GSS mRNA expression and IL-1, IL-6, TNF-α, JAK2, STAT3 and STA5 mRNA expression. Conclusion This study showed that the combination therapy of metformin and GA modulated JAK/STAT pathway mediated by the cytokines, and replenished glutathione in the pancreas of diabetic rats.
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    Polypharmacology of Gongronema latifolium leaf secondary metabolites against protein kinases implicated in Parkinson's disease and Alzheimer's disease
    (2021) Oyinloye BE; Iwaloye O; Ajiboye BO
    Neurodegenerative diseases (NDD) are one of the major health concerns around the globe; Parkinson's disease (PD) and Alzheimer's disease (AD) are the most prevalent form of NDD. Protein kinases (PKs), common protein domains implicated in neurodegenerative diseases, are regulatory protein of cell functions; and play a pivotal role in signal transduction. Hence, this study considered the computational screening of secondary metabolites form Gongronema latifolium leaf for their inhibitory activities against the three prevalent PKs leucine-rich repeat kinase 2 (LRRK2), GSK3β (glycogen kinase 3β) and MAPK14 associated with the onset of AD and PD. The compounds were initially screened against LRRK2, GSK3β and MAPK14 by molecular docking to retrieve the hits. Nine (9) compounds were chosen and calculated for binding free energy to determine their stability with the proteins. The Lipinski, Ghose, Veber and Egan rules were considered to predict the compounds drug-likeness, in addition to drug-drug interaction and GI absorption. 2D QSAR models were constructed using a Kernel-based PLS regression model with Canvas binary fingerprint as the X variable. From the selected nine-hit with favourable stability with the proteins, 4 flavonoids (Catechin, Gallocatechin, Butein and Isorhamnetin) showed drug-likeness attributes with a low tendency for drug-drug interaction and high GI absorption. The generated QSAR models also predicted moderate pIC50 values for these compounds against the three PKs. This study will help in future endeavours for finding effective therapy for AD and PD.